Optical: systems and elements – Compound lens system – Microscope
Reexamination Certificate
2001-06-20
2004-06-08
Robinson, Mark A. (Department: 2872)
Optical: systems and elements
Compound lens system
Microscope
C385S116000, C600S182000
Reexamination Certificate
active
06747795
ABSTRACT:
DESCRIPTION
The present invention relates to confocal microscopy, and relates particularly to confocal microscope having a parallel scanning system compatible with fiberoptics. The invention provides a remote probe for confocal imaging of tissue at locations within a body, such as commonly done with endoscopes, and thus the invention provides the advantages of confocal microscopy in biomedical applications by enabling access to distant and inconvenient regions.
The invention uses fiber optics, but in a way to provide significant improvement over confocal microscopes using fibers that have been reported, such as in which a single fiber serves as the source and the detector pinhole.
A line scanning confocal microscope with slit aperture detection can be regarded as a form of multifocal illumination and parallel detection, where all the foci line up in one direction. Image formation requires only slow scanning (at 25 or 30 Hz for video rate) in the second direction. This approach is particularly attractive because of its simplicity and high optical throughput. The major drawback of the line scanning approach is its relative poor rejection of unwanted photons compared to the pinhole system.
Briefly, the present invention provides a confocal microscope in which the region of interest (as for example a tissue ex-vivo, or in-vivo as inside a body cavity) is illuminated via a fiber optic bundle, where the spatial arrangement of fibers at one end of the bundle is different from that at the other end. Such a bundle is called an incoherent fiber optic bundle. A bundle in which the spatial arrangement of fibers is maintained is a coherent fiber bundle. The microscope may have means for scanning a laser beam from a slit providing an aperture in one direction across, as with a slit scanning microscope, but has true two-dimensional confocality because of encoding the slit with an incoherent fiber bundle. The incoherent bundle effectively multiplexes and demultiplexes the light, respectively, incident on and remitted from the region of interest. An important advantage of this microscope is that it can operate at the distal end of a fiber bundle and can therefore provide a probe on a flexible, small diameter member where it can be implemented on or as an endoscope or catheter.
It is a feature of the invention to provide an improved fiber optic confocal microscope where the fiber effects a parallel scanning mechanism that is inherently fiberoptic compatible and that retains the simplicity of the line scanning confocal microscope, while improving on its axial sectioning resolution. The improvement is provided by using an incoherent fiber bundle. In the bundle, the input and output fibers may be randomly arranged, although other, specific mapping can also be employed to obtain incoherent coupling via the fiber. A line source illuminates the proximal (P) end of the fiber bundle, which transforms the line input into disperse array of fibers at the distal (D) end, spread out over the whole bundle. This set of disperse spots is imaged onto the sample by an objective lens. Remitted light (fluorescence or back scattered) from the sample is collected and imaged by the same objective lens back onto the fiber endface (D), from a region in the sample being viewed, which is exactly in focus, the remitted light is imaged onto the same set of fibers which carried the illumination light, and transformed back into a line at (P). For an unwanted (or out-of-focus) sample plane, each illuminated fiber at D will produce, on the return, a smeared-out spot, which covers not just the original fiber but a group of surrounding fibers. For spots illuminated indirectly, such as by scattered light, the same is true. Back at Plane P, the fibers which carry the “smeared-out” photons do not reassemble into a line but are spread out dispersely over the bundle. A slit aperture, placed at a plane conjugate to P, allows only light (photons) from the in-focus plane, and intentionally illuminated spots, to pass through the detector, while rejecting most of the unwanted photons. The detector provides signals representing scan lines in the plane from which a 2-D image at that plane can be constructed.
REFERENCES:
patent: 4806004 (1989-02-01), Wayland
patent: 5120953 (1992-06-01), Harris
patent: 5122653 (1992-06-01), Ohki
patent: 5304173 (1994-04-01), Kittrell et al.
patent: 5323009 (1994-06-01), Harris
patent: 5450203 (1995-09-01), Penkethman
patent: 5785651 (1998-07-01), Kuhn et al.
patent: 6121603 (2000-09-01), Hang et al.
patent: 6370422 (2002-04-01), Richards-Kortum et al.
patent: 6663560 (2003-12-01), MacAulay et al.
patent: WO 99/44089 (1999-09-01), None
patent: WO 99/47041 (1999-09-01), None
D. R. Sandison and W. W. Webb, Background Rejection and Signal-to-noise Optimization in Confocal and Alternative Fluorescence Microscopes, Appl. Opt., vol. 33, No. 4, 603-615 (1994).
J. Bewersdorf, R. Pick, and S. W. Hell, Multifocal Multiphoton Microscopy, Opt., vol. 23, 655-659 (1998).
R. Juskkaitis and T. Wilson, Direct-view Fiber-optic Confocal Microscope, Opt. Lett., vol. 19, No. 22, 1906-1908 (1994).
P. M. Delaney, M. R. Harris, and R. G. King, Fiber-optic Laser Scanning Confocal Microscope Suitable for Fluorescence Imaging, Appl. Opt., vol. 33, No. 4, 573-577 (1994).
D. L. Dickensheets and G. S. Kino, Micromachined Scanning Confocal Optical Microscope, Opt. Lett. vol. 21, No. 10, 764-766, (1996).
A. F. Gmitro and D. Aziz, Confocal Microscopy Through a Fiber-optic Imaging Bundle, Opt. Lett. vol. 18, No. 8, 565-567 (1993).
Y. S. Sabharwal, A. R. Rouse, L. Donaldson, M. F. Hopkins, and A. F. Gmitro, Slit-scanning Confocal Microendoscope For High-resolution in vivo Imaging, Appl. Opt., vol. 38, No. 34, 7133-7144 (1999).
G. Q. Xiao, T. R. Corle, and G. S. Kino, Real-Time Confocal Scanning Optical Microscope, Appl. Phys. Lett., vol. 53, No. 8, 716-718 (1988).
A. H. Buist, M. Muller, J. Squier, and G. J. Brakenhoff, Real Time Two-photon Absorption Microscopy Using Multi Point Excitation, J. Microsc. (Oxford) Part 2, vol. 192, 217-226 (1998).
G. J. Tearney, R. H. Webb, and B. E. Bourma, Spectrally Encoded Confocal Microscopy, Opt. Lett., vol. 23, No. 15, 1152-1154 (1998).
C. J. Koester, J. D. Auran, H. D. Rosskothen, G. J. Florakis, and R. B. Tackaberry, Clinical Microscopy of the Cornea Utilizing Optical Sectioning and a High-Numerical-Aperture Objective, J. Opt. Soc. Am. A, vol. 10, No. 7, 1670-1679 (1993).
G. J. Brakenhoff and K. Visscher, Confocal Imaging with Bilateral Scanning and Array Detectors, J. Microsc. (Oxford) Part 1, vol. 165, 139-146 (1992).
Lin et al. “Fiber-Coupled Multiplexed Confocal Microscope,” Optics Letters, Optical Society of America, Washington, US, vol. 25, No. 13, Jul. 1, 2000, pp. 954-956.
Lin Charles P.
Webb Robert H.
Fineman Lee
Frommer & Lawrence & Haug LLP
Kowalski Thomas J.
Leahy Amy
The General Hospital Corporation
LandOfFree
Fiber-coupled multiplexed confocal microscope does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Fiber-coupled multiplexed confocal microscope, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Fiber-coupled multiplexed confocal microscope will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3343995